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- PDB-8ro2: Integrative Structure of the human intron lariat Spliceosome (ILS'') -
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Open data
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Basic information
Entry | Database: PDB / ID: 8ro2 | ||||||
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Title | Integrative Structure of the human intron lariat Spliceosome (ILS'') | ||||||
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![]() | SPLICING / mRNA / intron lariat spliceosome / pre-mRNA | ||||||
Function / homology | ![]() RNA lariat debranching enzyme activator activity / spliceosomal complex disassembly / post-spliceosomal complex / biomineral tissue development / negative regulation of double-strand break repair via nonhomologous end joining / U2-type post-mRNA release spliceosomal complex / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / regulation of retinoic acid receptor signaling pathway / positive regulation of myoblast proliferation ...RNA lariat debranching enzyme activator activity / spliceosomal complex disassembly / post-spliceosomal complex / biomineral tissue development / negative regulation of double-strand break repair via nonhomologous end joining / U2-type post-mRNA release spliceosomal complex / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / regulation of retinoic acid receptor signaling pathway / positive regulation of myoblast proliferation / post-mRNA release spliceosomal complex / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / 3'-5' RNA helicase activity / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / U7 snRNP / generation of catalytic spliceosome for first transesterification step / histone methyltransferase binding / histone pre-mRNA 3'end processing complex / alternative mRNA splicing, via spliceosome / regulation of vitamin D receptor signaling pathway / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / response to alkaloid / nuclear retinoic acid receptor binding / embryonic brain development / protein methylation / U12-type spliceosomal complex / oocyte development / 7-methylguanosine cap hypermethylation / RNA splicing, via transesterification reactions / U1 snRNP binding / mRNA 3'-end processing / sno(s)RNA-containing ribonucleoprotein complex / methylosome / ATP-dependent activity, acting on RNA / pICln-Sm protein complex / U2-type catalytic step 1 spliceosome / pre-mRNA binding / positive regulation of mRNA splicing, via spliceosome / snRNP binding / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / P granule / host-mediated activation of viral transcription / spliceosomal tri-snRNP complex / U2-type precatalytic spliceosome / telomerase holoenzyme complex / U2-type spliceosomal complex / positive regulation of vitamin D receptor signaling pathway / telomerase RNA binding / commitment complex / mRNA cis splicing, via spliceosome / U2-type prespliceosome assembly / nuclear vitamin D receptor binding / Transport of Mature mRNA derived from an Intron-Containing Transcript / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Notch binding / RUNX3 regulates NOTCH signaling / U2-type catalytic step 2 spliceosome / positive regulation of neurogenesis / NOTCH4 Intracellular Domain Regulates Transcription / U4 snRNP / U2 snRNP / RNA Polymerase II Transcription Termination / U1 snRNP / NOTCH3 Intracellular Domain Regulates Transcription / protein peptidyl-prolyl isomerization / U2-type prespliceosome / inner cell mass cell proliferation / WD40-repeat domain binding / ubiquitin-ubiquitin ligase activity / nuclear androgen receptor binding / K63-linked polyubiquitin modification-dependent protein binding / precatalytic spliceosome / snoRNA binding / muscle organ development / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / generation of catalytic spliceosome for second transesterification step / lipid biosynthetic process / Notch-HLH transcription pathway / Formation of paraxial mesoderm / SMAD binding / positive regulation of transforming growth factor beta receptor signaling pathway / spliceosomal complex assembly / mitotic G2 DNA damage checkpoint signaling / mRNA Splicing - Minor Pathway / mRNA 3'-splice site recognition / spliceosomal tri-snRNP complex assembly / Prp19 complex / blastocyst development / protein K63-linked ubiquitination / U5 snRNA binding / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / U5 snRNP / protein localization to nucleus / positive regulation of G1/S transition of mitotic cell cycle / embryonic organ development Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Rothe, P. / Vorlaender, M.K. / Plaschka, C. | ||||||
Funding support | European Union, 1items
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![]() | ![]() Title: Mechanism for the initiation of spliceosome disassembly. Authors: Matthias K Vorländer / Patricia Rothe / Justus Kleifeld / Eric D Cormack / Lalitha Veleti / Daria Riabov-Bassat / Laura Fin / Alex W Phillips / Luisa Cochella / Clemens Plaschka / ![]() ![]() Abstract: Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on ...Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodelling for catalysis, but the mechanism of disassembly remains unclear. Here we report cryo-electron microscopy structures of nematode and human terminal intron lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 therefore controls both the start and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 2.1 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 247 KB | Display | |
Data in CIF | ![]() | 423.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 19399MC ![]() 8ro0C ![]() 8ro1C ![]() 9fmdC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-RNA chain , 4 types, 4 molecules 265IN
#1: RNA chain | Mass: 60186.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: RNA chain | Mass: 34098.270 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#26: RNA chain | Mass: 36908.668 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#29: RNA chain | Mass: 30153.607 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 18 types, 18 molecules CDXEJNQRSZz3ALPPXTTFb
#3: Protein | Mass: 109560.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#5: Protein | Mass: 91065.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#6: Protein | Mass: 39359.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#7: Protein | Mass: 100610.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#10: Protein | Mass: 17032.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#12: Protein | Mass: 171502.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#13: Protein | Mass: 61770.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#14: Protein | Mass: 18257.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#16: Protein | Mass: 19223.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#24: Protein | Mass: 49818.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#25: Protein | Mass: 52639.953 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#27: Protein | Mass: 273974.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#30: Protein | Mass: 92406.883 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#33: Protein | Mass: 26674.447 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#34: Protein | Mass: 104953.656 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#35: Protein | Mass: 57280.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#36: Protein | Mass: 96945.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#37: Protein | Mass: 24642.131 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Pre-mRNA-splicing factor ... , 5 types, 5 molecules DKOIM
#4: Protein | Mass: 33046.254 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#8: Protein | Mass: 26163.420 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#11: Protein | Mass: 46959.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#28: Protein | Mass: 100148.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#32: Protein | Mass: 28780.518 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-CWF19-like protein ... , 2 types, 2 molecules L1L2
#9: Protein | Mass: 60696.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#31: Protein | Mass: 103976.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Pre-mRNA-processing factor ... , 2 types, 5 molecules Wsqrt
#15: Protein | Mass: 65612.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#23: Protein | Mass: 55245.547 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: Q9UMS4, RING-type E3 ubiquitin transferase |
-Small nuclear ribonucleoprotein ... , 6 types, 6 molecules acdefg
#17: Protein | Mass: 13940.308 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#18: Protein | Mass: 13310.653 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#19: Protein | Mass: 13551.928 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#20: Protein | Mass: 10817.601 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#21: Protein | Mass: 9734.171 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#22: Protein | Mass: 8508.084 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 3 types, 5 molecules 




#38: Chemical | ChemComp-GTP / | ||
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#39: Chemical | #40: Chemical | ChemComp-IHP / | |
-Details
Has ligand of interest | N |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human Intron-lariat splicoesome / Type: COMPLEX Entity ID: #1, #25-#26, #2, #27, #3-#6, #28-#29, #7-#8, #30, #9, #31-#32, #10-#11, #33-#34, #12-#14, #35-#36, #15-#17, #37, #18-#24 Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.9 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 750 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 87951 / Symmetry type: POINT |